Research into Alzheimer’s disease has long focused on understanding the role of two key proteins, beta amyloid and the tau protein. Found in tangles in patients’ brain tissue, a pathological form of the tau protein contributes to propagating the disease in the brain.

In new research from their joint laboratory, Judith Steen, PhD, and Hanno Steen, PhD show for the first time that this pathological tau protein changes its forms over time, which could mean it will take multiple drugs to target it effectively.

For years, pharmaceutical companies have largely focused with very limited success on developing Alzheimer’s drugs against beta amyloid. More recently, drug discovery has shifted to drugs against tau. This new tau discovery may help prevent the same fate for drugs now in development against tau because it shows that the protein may present with one set of targets at early stages, with other targets at later stages in the disease process.

“The tau protein in Alzheimer’s disease looks different at every stage,” says lead investigator Judith Steen. “We discovered that tau undergoes a series of chemical modifications in a stepwise process that correlates with disease severity. This suggests that we need to have different diagnostics and treatments for every stage of disease.”